Sample Required?

Test Preparation Needed?

How is it used?

Cystatin C may be used as an alternative to creatinine and creatinine clearance to screen for and monitor kidney dysfunction in those with known or suspected kidney disease. It may be especially useful in those cases where creatinine measurement is not appropriate, for instance, in those who have liver cirrhosis, are very obese, are malnourished, or have reduced muscle mass. Measuring cystatin C may also be useful in the early detection of kidney disease when other test results may still be normal and an affected person may have few, if any, symptoms.

Researchers are exploring other uses of cystatin C, such as using it alone or in combination with blood creatinine for estimating the glomerular filtration rate (GFR). A recent study found that an equation for eGFR that includes both creatinine and cystatin C was more accurate than one that uses either of these alone and could be used to confirm chronic kidney disease (CKD) in people with an eGFR near 60, the threshold for CKD. In addition to kidney dysfunction, it has been associated with an increased risk of cardiovascular disease and heart failure in older adults.

When is it ordered?

Cystatin C is gaining acceptance as studies confirm and define its usefulness, especially as an early, sensitive marker for chronic kidney disease (CKD). It may be ordered when a person has a known or suspected disease that affects or potentially affects kidney function and reduces the rate at which the kidneys filter impurities from the blood, the glomerular filtration rate (GFR). It may be ordered when a health practitioner is not satisfied with the results of other tests, such as a creatinine or creatinine clearance, or wants to check for early kidney dysfunction, particularly in the elderly, and/or wants to monitor known impairment over time.

Research is ongoing to learn more about cystatin C as an indicator of risk of end stage renal disease, heart failure, and death. Studies have also found that, in diverse populations, cystatin C may improve the estimate of GFR when combined in an equation with blood creatinine.

What does the test result mean?

An high level of cystatin C in the blood corresponds to a decreased glomerular filtration rate (GFR) and hence to kidney dysfunction. Since cystatin C is produced throughout the body at a constant rate and removed and broken down by the kidneys, it should remain at a steady level in the blood if the kidneys are working efficiently and the GFR is normal.

Recent studies suggest that increased levels of cystatin C may also indicate an increased risk of heart disease, heart failure, stroke, and mortality.

Is there anything else I should know?

Cystatin C has been associated with hyperhomocysteinemia (increased homocysteine), which is often found in kidney transplant patients, and it has been shown to increase with the progression of liver disease. At least one study has looked at comparing cystatin C levels in serum with that found in pleural effusion to help determine the cause of the effusion. These associations may or may not prove clinically useful.

In the absence of kidney disease, cystatin C levels may be elevated in rheumatic diseases and in malignant diseases, although they are not affected by tumor burden, the amount of cancer that someone has.

What is being tested?

Cystatin C is a relatively small protein that is produced throughout the body by all cells that contain a nucleus and is found in a variety of body fluids, including the blood. It is produced, filtered from the blood by the kidneys, and broken down at a constant rate. This test measures the amount of cystatin C in blood to help evaluate kidney function.

Cystatin C is filtered out of the blood by the glomeruli, clusters of tiny blood vessels in the kidneys that allow water, dissolved substances, and wastes to pass through their walls while retaining blood cells and larger proteins. What passes through the walls of the glomeruli forms a filtrate fluid. From this fluid, the kidneys reabsorb cystatin C, glucose, and other substances. The remaining fluid and wastes are carried to the bladder and excreted as urine. The reabsorbed cystatin C is then broken down and is not returned to the blood.

The rate at which the fluid is filtered is called the glomerular filtration rate (GFR). A decline in kidney function leads to decreases in the GFR and to increases in cystatin C and waste products such as creatinine in the blood.

When the kidneys are functioning normally, concentrations of cystatin C in the blood are stable, but as kidney function deteriorates, the concentrations begin to rise. This increase occurs as the GFR falls and is often detectable before there is a measurable decrease in the GFR.

Because cystatin C levels fluctuate with changes in GFR, there has been interest in the cystatin C test as one method of evaluating kidney function. Tests currently used include creatinine, a byproduct of muscle metabolism that is measured in the blood and urine, blood urea nitrogen (BUN), and eGFR (an estimate of the GFR usually calculated from the blood creatinine level). Unlike creatinine, cystatin C is not significantly affected by muscle mass (hence, sex or age), race, or diet, which has led to the idea that it could be a more reliable marker of kidney function and potentially used to generate a more precise estimate of GFR.

While there are growing data and literature supporting the use of cystatin C, there is still a degree of uncertainty about when and how it should be used. However, testing is becoming increasingly more available and steps are being taken toward standardizing the calibration of cystatin C results.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No. Unlike creatinine, cystatin C is reabsorbed from the glomerular filtrate and then metabolized in the kidneys. Under normal conditions, cystatin C is not found at detectable levels in the urine.

How is an eGFR calculated?

The most commonly used equation for calculating the eGFR, and the one currently recommended by the National Kidney Foundation (NKF) for general use, is called the MDRD (Modification of Diet in Renal Disease Study) equation. It requires a person's serum creatinine, age, and assigned values based upon sex and race.

According to the NKF, as of January 2013, many large commercial clinical laboratories have changed from using the MDRD equation for eGFR reporting to a slightly different one that uses the same factors, the CKD-EPI equation, published in 2009. The results reported using one equation versus the other will not be identical but should give the health practitioner similar information.

Researchers are also evaluating the usefulness of a variety of other equations to estimate GFR that combine tests such as a creatinine, BUN, and/or cystatin C.

How can my actual GFR be determined?

The best method for directly determining the glomerular filtration rate (GFR) is a procedure called an "inulin clearance." It involves introducing a fluid containing the marker molecule inulin (NOT insulin) into your veins (IV - intravenous infusion) and then collecting timed urine samples over a period of hours. The urine volumes are noted and the inulin in each sample is measured to allow determination of the GFR. This test and other methods of determining GFR, such as those that use radioactive markers, are not routinely ordered and are primarily performed in research settings.

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Descriptions of clinical laboratory tests were originally prepared for use on Lab Tests Online, an award-winning patient education website on clinical laboratory testing. Lab Tests Online is produced by the American Association for Clinical Chemistry (AACC), a global scientific and medical professional organization dedicated to clinical laboratory science and its application to healthcare. The Lab Tests Online website is developed in collaboration with other laboratory professional societies and is funded in part through corporate sponsorships.